Project Summary/Abstract The ability of the mammalian brain to store and later retrieve information is remarkable. Detailed, complex memories can be formed after as little as one exposure, and those memories can be retained for decades. This ability is compromised following damage to the hippocampus, and interaction between the hippocampus and the neocortex is thought to be critical for systems memory consolidation. Impaired memory is a debilitating consequence of diseases such as temporal lobe epilepsy, Alzheimer's disease, depression, and schizophrenia that collectively affect over twenty-five million Americans. However, our understanding of the circuit mechanisms that support memory consolidation and rapid new learning is incomplete, particularly in the primate brain. Our long-range goal is to contribute to a better understanding of the neural mechanisms that underlie memory processes to bring us closer to developing new therapies for these disabled patients. Psychological theories and behavioral studies have suggested that rapid, single-trial accumulation of information is facilitated by prior knowledge, a ?mental schema? that provides a framework onto which new information can be assimilated. The hippocampus is considered to be critical for extracting and representing regularities that hold across learning episodes, and these regularities constitute the cognitive schema. Determining how the hippocampus supports this cognitive framework will be critical to understanding the hippocampal-neocortical interactions that are necessary for memory consolidation. The experiments proposed here will directly examine hippocampal-cortical interactions during learning and consolidation. We propose to utilize newly available technical developments to advance our understanding of the mechanism that support rapid new learning. Specifically, we propose to perform large-scale recordings from individual neurons throughout the hippocampus, parietal cortex, and prefrontal cortex in monkeys trained to perform a task of object-place association in virtual environments. We will use stable and unstable environments to examine the impact of a schema on association learning and neural activity, and we will track neural activity during learning to investigate the mechanisms that support the formation of a schema. The proposed experiments have the following potential outcomes: 1) to identify the network activity across single units in the hippocampus, parietal and prefrontal cortex in support of object-place association learning, 2) to identify the dynamics of cross- regional communication through synchronized oscillatory activity during schema development and rapid learning, and 3) to identify hippocampal-cortical interaction during sleep and quiet wakefulness and determine how this interaction impacts memory consolidation.